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Alzheimer's Disease (AD) is a global health issue, affecting over 6 million in the United States, with that number expected to increase as the aging population grows. As a neurodegenerative disorder that affects memory and cognitive functions, it is well established that AD is associated with cardiovascular risk factors beyond only cerebral decline. However, the study of cerebrovascular techniques for AD is still evolving. Here, we provide reproducible methods to measure impedance-based pulse wave velocity (PWV), a marker of arterial stiffness, in the systemic vascular (aortic PWV) and in the cerebral vascular (cerebral PWV) systems. Using aortic impedance and this relatively novel technique of cerebral impedance to comprehensively describe the systemic vascular and the cerebral vascular systems, we examined the sex-dependent differences in 5x transgenic mice (5XFAD) with AD under normal and high-fat diet, and in wild-type mice under a normal diet. Additionally, we validated our method for measuring cerebrovascular impedance in a model of induced stress in 5XFAD. Together, our results show that sex and diet differences in wildtype and 5XFAD mice account for very minimal differences in cerebral impedance. Interestingly, 5XFAD, and not wildtype, male mice on a chow diet show higher cerebral impedance, suggesting pathological differences. Opposingly, when we subjected 5XFAD mice to stress, we found that females showed elevated cerebral impedance. Using this validated method of measuring impedance-based aortic and cerebral PWV, future research may explore the effects of modifying factors including age, chronic diet, and acute stress, which may mediate cardiovascular risk in AD.

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PURPOSE OF REVIEW: Pulse wave velocity (PWV) is an important and well-established measure of arterial stiffness that is strongly associated with aging. Age-related alterations in the elastic properties and integrity of arterial walls can lead to cardiovascular disease. PWV measurements play an important role in the early detection of these changes, as well as other cardiovascular disease risk factors, such as hypertension. This review provides a comprehensive summary of the current knowledge of the effects of aging on arterial stiffness, as measured by PWV. RECENT FINDINGS: This review highlights recent findings showing the applicability of PWV analysis for investigating heart failure, hypertension, and other cardiovascular diseases, as well as cerebrovascular diseases and Alzheimer's disease. It also discusses the clinical implications of utilizing PWV to monitor treatment outcomes, various challenges in implementing PWV assessment in clinical practice, and the development of new technologies, including machine learning and artificial intelligence, which may improve the usefulness of PWV measurements in the future. Measuring arterial stiffness through PWV remains an important technique to study aging, especially as the technology continues to evolve. There is a clear need to leverage PWV to identify interventions that mitigate age-related increases in PWV, potentially improving CVD outcomes and promoting healthy vascular aging.

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During aging, muscle gradually undergoes sarcopenia, the loss of function associated with loss of mass, strength, endurance, and oxidative capacity. However, the 3D structural alterations of mitochondria associated with aging in skeletal muscle and cardiac tissues are not well described. Although mitochondrial aging is associated with decreased mitochondrial capacity, the genes responsible for the morphological changes in mitochondria during aging are poorly characterized. We measured changes in mitochondrial morphology in aged murine gastrocnemius, soleus, and cardiac tissues using serial block-face scanning electron microscopy and 3D reconstructions. We also used reverse transcriptase-quantitative PCR, transmission electron microscopy quantification, Seahorse analysis, and metabolomics and lipidomics to measure changes in mitochondrial morphology and function after loss of mitochondria contact site and cristae organizing system (MICOS) complex genes, Chchd3, Chchd6, and Mitofilin. We identified significant changes in mitochondrial size in aged murine gastrocnemius, soleus, and cardiac tissues. We found that both age-related loss of the MICOS complex and knockouts of MICOS genes in mice altered mitochondrial morphology. Given the critical role of mitochondria in maintaining cellular metabolism, we characterized the metabolomes and lipidomes of young and aged mouse tissues, which showed profound alterations consistent with changes in membrane integrity, supporting our observations of age-related changes in muscle tissues. We found a relationship between changes in the MICOS complex and aging. Thus, it is important to understand the mechanisms that underlie the tissue-dependent 3D mitochondrial phenotypic changes that occur in aging and the evolutionary conservation of these mechanisms between Drosophila and mammals.

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With sparse treatment options, cardiac disease remains a significant cause of death among humans. As a person ages, mitochondria breakdown and the heart becomes less efficient. Heart failure is linked to many mitochondria-associated processes, including endoplasmic reticulum stress, mitochondrial bioenergetics, insulin signaling, autophagy, and oxidative stress. The roles of key mitochondrial complexes that dictate the ultrastructure, such as the mitochondrial contact site and cristae organizing system (MICOS), in aging cardiac muscle are poorly understood. To better understand the cause of age-related alteration in mitochondrial structure in cardiac muscle, we used transmission electron microscopy (TEM) and serial block facing-scanning electron microscopy (SBF-SEM) to quantitatively analyze the three-dimensional (3-D) networks in cardiac muscle samples of male mice at aging intervals of 3 mo, 1 yr, and 2 yr. Here, we present the loss of cristae morphology, the inner folds of the mitochondria, across age. In conjunction with this, the three-dimensional (3-D) volume of mitochondria decreased. These findings mimicked observed phenotypes in murine cardiac fibroblasts with CRISPR/Cas9 knockout of Mitofilin, Chchd3, Chchd6 (some members of the MICOS complex), and Opa1, which showed poorer oxidative consumption rate and mitochondria with decreased mitochondrial length and volume. In combination, these data show the need to explore if loss of the MICOS complex in the heart may be involved in age-associated mitochondrial and cristae structural changes.NEW & NOTEWORTHY This article shows how mitochondria in murine cardiac changes, importantly elucidating age-related changes. It also is the first to show that the MICOS complex may play a role in outer membrane mitochondrial structure.

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Introduction: Heart failure (HF) is the leading cause of death worldwide. Most large and small animal disease models of HF are based on surgical procedures. A common surgical technique to induce HF is transverse aortic constriction (TAC), which induces pressure overload. The conventional TAC (cTAC) procedure is a highly invasive surgery that is associated with severe inflammation and excessive perioperative deaths. Aim: To establish an improved, minimally invasive TAC (mTAC) procedure that does not require thoracotomy. Methods and results: Following anesthesia, mice were intubated, and a small incision was made at the neck and chest. After cutting the sternum about 4 mm, the aortic arch was approached without opening the pleural cavity. A suture was placed between the brachiocephalic artery and the left common carotid artery. This model was associated with low perioperative mortality and a highly reproducible constriction evidenced by an increased right-to-left carotid blood flow velocity ratio in mTAC mice (5.9 ± 0.2) vs. sham controls (1.2 ± 0.1; P < 0.001). mTAC mice exhibited progressive cardiac remodeling during the 8 weeks post-TAC, resulting in reduced left ventricular (LV) contractility, increased LV end-systolic diameter, left atrial enlargement and diastolic dysfunction, and an increased heart weight to tibia length ratio (mTAC: 15.0 ± 0.8 vs. sham: 10.1 ± 0.6; P < 0.01). Conclusion: Our data show that the mTAC procedure yields a highly reproducible phenotype consisting of LV contractile dysfunction and enlargement, combined with left atrial enlargement and diastolic dysfunction. Potential impact of the findings: This model may be used to test the molecular mechanisms underlying atrial remodeling associated with HF development or to evaluate therapeutic strategies to treat these conditions.

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We analyzed the effect of a single nucleotide polymorphism, g. C3141T in the 3' UTR of Signal transducer and activator of transcription-1 gene (STAT1) on milk production traits in the Holstein Friesian crossbred cattle of Kerala (n = 144) by association analysis and expression study. The population was genotyped by restriction fragment length polymorphism using Pag1. Association study using the General Linear Model-Analysis of Variance revealed that none of the yield or composition traits analyzed were significantly differed. The expression profile of STAT1 gene in leucocytes of animals bearing homozygous genotypes was compared by quantitative real time PCR using SYBR green chemistry with and relative expression was not found to be significantly differed. The second stage of the study, the STAT1 mRNA spanning 3213 bp was amplified from leucocytes and sequenced (GenBank: MT459802.1). Two novel SNPs were identified; one synonymous mutation in the coding region (g.A1212G) and the other in the 3'UTR (g.T3042C). The novel SNPs might contribute to STAT1 gene regulation mediated by alternate spicing or binding sites for regulatory molecules. The results reiterate the importance of extensive studies of STAT1 gene variants to substantiate the presence of a quantitative trait loci for dairy traits in the vicinity of STAT1 gene.

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Introduction: Many studies in mice have demonstrated that cardiac-specific innate immune signaling pathways can be reprogrammed to modulate inflammation in response to myocardial injury and improve outcomes. While the echocardiography standard parameters of left ventricular (LV) ejection fraction, fractional shortening, end-diastolic diameter, and others are used to assess cardiac function, their dependency on loading conditions somewhat limits their utility in completely reflecting the contractile function and global cardiovascular efficiency of the heart. A true measure of global cardiovascular efficiency should include the interaction between the ventricle and the aorta (ventricular-vascular coupling, VVC) as well as measures of aortic impedance and pulse wave velocity. Methods: We measured cardiac Doppler velocities, blood pressures, along with VVC, aortic impedance, and pulse wave velocity to evaluate global cardiac function in a mouse model of cardiac-restricted low levels of TRAF2 overexpression that conferred cytoprotection in the heart. Results: While previous studies reported that response to myocardial infarction and reperfusion was improved in the TRAF2 overexpressed mice, we found that TRAF2 mice had significantly lower cardiac systolic velocities and accelerations, diastolic atrial velocity, aortic pressures, rate-pressure product, LV contractility and relaxation, and stroke work when compared to littermate control mice. Also, we found significantly longer aortic ejection time, isovolumic contraction and relaxation times, and significantly higher mitral early/atrial ratio, myocardial performance index, and ventricular vascular coupling in the TRAF2 overexpression mice compared to their littermate controls. We found no significant differences in the aortic impedance and pulse wave velocity. Discussion: While the reported tolerance to ischemic insults in TRAF2 overexpression mice may suggest enhanced cardiac reserve, our results indicate diminished cardiac function in these mice.

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Cattle belonging to seven different genetic groups in Kerala state, India were chosen for the study to find out the genetic diversity between the groups, which would aid in their sustainable improvement and conservation of native cattle. They included the native groups namely, Vechur, Kasaragod, Vadakara dwarf and Vilwadri, along with three different grades of crossbred cattle, based on milk production. Genomic DNA was isolated from 20 to 30 unrelated animals of each group and a panel of 25 microsatellite markers as suggested by FAO-ISAG, were amplified by multiplex PCR. The PCR amplicons were genotyped and the allelic data analyzed using suitable Bioinformatics softwares. The present study showed that the observed number of alleles was much more than the expected, in all populations. The mean PIC value obtained for the present study was 0.8912 and increased number of private alleles were observed, especially in Vilwadri and Kasaragod groups. Negative value of FIS (-0.055) indicated that the level of inbreeding was less. The FST value was 0.1442 indicating that the populations showed good genetic differentiation. The results of Structure analysis revealed admixture only in Vadakara population. The results obtained from the present study showed that Vilwadri and Kasaragod cattle showed distinct differences from other groups.

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The incidence of diastolic dysfunction increases with age in both humans and mice. This is characterized by increased passive stiffness and slower relaxation of the left ventricle. The stiffness arises at least partially from progressively increased interstitial collagen deposition because of highly secretory fibroblasts. In the past, we demonstrated that AMPK activation via the drug 5-aminoimidazole-4-carboxamide riboside (AICAR) in middle-aged mice reduced adverse remodeling after myocardial infarction. Therefore, as an attempt to normalize the fibroblast phenotype, we used 21-mo-old male and female mice and treated them with AICAR (0.166 mg/g body wt) where each mouse was followed in a functional study over a 3-mo period. We found sex-related differences in extracellular matrix (ECM) composition as well as heart function indices at baseline, which were further accentuated by AICAR treatment. AICAR attenuated the age-related increase in left atrial volume (LAV, an indicator of diastolic dysfunction) in female but not in male hearts, which was associated with reduced collagen deposition in the old female heart, and reduced the transcription factor Gli1 expression in cardiac fibroblasts. We further demonstrated that collagen synthesis was dependent on Gli1, which is a target of AMPK-mediated degradation. By contrast, AICAR had a minor impact on cardiac fibroblasts in the old male heart because of blunted AMPK phosphorylation. Hence, it did not significantly improve old male heart function indices. In conclusion, we demonstrated that male and female hearts are phenotypically different, and sex-specific differences need to be considered when analyzing the response to pharmacological intervention.NEW & NOTEWORTHY The aging heart develops diastolic dysfunction because of increased collagen deposition. We attempted to reduce collagen expression in the old heart by activating AMPK using AICAR. An improvement of diastolic function and reduction of cardiac fibrosis was found only in the female heart and correlated with decreased procollagen expression and increased degradation of the transcription factor Gli1. Male hearts display blunted AICAR-dependent AMPK activation and therefore this treatment had no benefits for the male mice.

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Leukemia is usually diagnosed by viewing the smears of blood and bone marrow using microscopes and complex Cytochemical tests can be used to authorize and classify leukemia. But these methods are costly, slow and affected by the proficiency and expertise of the specialists concerned. Leukemia can be detected with the help of image processing-based methods by analyzing microscopic smear images to detect the presence of leukemic cells and such techniques are simple, fast, cheap and not biased by the specialists. The proposed study presents a computer aided diagnosis system that uses pretrained deep Convolutional Neural Networks (CNNs) for detection of leukemia images against normal images. The use of pretrained networks is comparatively an easy method of applying deep learning for image analysis and the comparison results of the present study can be used to choose appropriate networks for diagnostic tasks. The microscopic images used in the proposed work were downloaded from a public dataset ALL-IDB. In the proposed work, image classification is done without using any image segregation and feature extraction practices and the study used pretrained series network AlexNet, VGG-16, VGG-19, Directed Acyclic Graph (DAG) networks GoogLeNet, Inceptionv3, MobileNet-v2, Xception, DenseNet-201, Inception-ResNet-v2 and residual networks ResNet-18, ResNet-50 and ResNet-101 for performing the classification and comparison. A classification accuracy of 100% is obtained with all the pretrained networks used in the study for ALL_IDB1 dataset and for ALL_IDB2 dataset, 100% accuracy is obtained with all networks except the AlexNet and VGG-16. The efficacy of three optimization algorithms Stochastic Gradient Descent with Momentum (SGDM), Root Mean Square propagation (RMSprop) and Adaptive Moment estimation (ADAM) is also compared in all the classifications performed. The study considered the detection of leukemia in general only, and classification of leukemia into different types can be attempted as a future work.

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The maximum value of the first derivative of the invasively measured left ventricular (LV) pressure (+ dP/dtmax or P') is often used to quantify LV contractility, which in mice is limited to a single terminal study. Thus, determination of P' in mouse longitudinal/serial studies requires a group of mice at each desired time point resulting in "pseudo" serial measurements. Alternatively, a noninvasive surrogate for P' will allow for repeated measurements on the same group of mice, thereby minimizing physiological variability and requiring fewer animals. In this study we evaluated aortic acceleration and other parameters of aortic flow velocity as noninvasive indices of LV contractility in mice. We simultaneously measured LV pressure invasively with an intravascular pressure catheter and aortic flow velocity noninvasively with a pulsed Doppler probe in mice, at baseline and after the administration of the positive inotrope, dobutamine. Regression analysis of P' versus peak aortic velocity (vp), peak velocity squared/rise time (vp2/T), peak (+ dvp/dt or v'p) and mean (+ dvm/dt or v'm) aortic acceleration showed a high degree of association (P' versus: vp, r2 = 0.77; vp2/T, r2 = 0.86; v'p, r2 = 0.80; and v'm, r2 = 0.89). The results suggest that mean or peak aortic acceleration or the other parameters may be used as a noninvasive index of LV contractility.

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OBJECTIVES: The presence of comorbidities such as cardiovascular disease, peripheral vascular disease, and chronic renal disease, or and the prevention of these ailments in diabetics, frequently demands multiple drug treatments, increasing the risk of drug-drug interactions (DDIs). The current study was focused on identifying possible DDIs on concomitant administration of losartan, a drug used to regulate hypertension along with a combination of glimepiride + metformin, widely used to treat diabetes mellitus. Possible pharmacodynamic and pharmacokinetic interactions were observed for, following single-dose as well as multiple-dose treatment protocols in normal and alloxan-induced diabetes in albino Wistar rats and rabbits. MATERIALS AND METHODS: Blood samples from surviving rats/rabbits obtained through orbital venous sinus bleeding/marginal ear vein bleeding, respectively, at predetermined intervals and put through to biochemical estimations of sugar level in the blood by Glucose oxidase/peroxidase method; insulin levels in serum using the enzyme-linked immunosorbent assay and serum glimepiride levels using the high-performance liquid chromatography. RESULTS AND DISCUSSION: Losartan, when treated as a single drug, resulted in a slight lowering of blood glucose levels in normal rats, diabetic rats and normal rabbits. Hypoglycemic activity of a combination of glimepiride + metformin was enhanced when losartan was co-administered as a single dosage schedule as well as a multiple dose schedule as indicated by a reduced blood glucose level and enhanced levels of insulin in rats as well as in rabbits. Serum glimepiride levels were also higher and pharmacokinetic parameters of glimepiride including mean residence time, Cmax, T1/2, AUMC0-∞, AUMC0-t, and AUC0-∞, were significantly higher, whereas its clearance was decreased in the two regimens of losartan that was followed. CONCLUSION: It can therefore be concluded, that in diabetics with hypertension as a comorbidity condition, co-administration of losartan with glimepiride + metformin should be avoided or the dosage of a combination of glimepiride + metformin needs to be tittered to avoid recurrence of hypoglycemic episodes.

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Diastolic dysfunction is condition of a stiff ventricle and a function of aging. It causes significant cardiovascular mortality and morbidity, and in fact, three million Americans are currently suffering from this condition. To date, all the pharmacological clinical trials have been negative. The lack of success in attenuating/ameliorating diastolic dysfunction stems from lack of duplication of myriads of clinical manifestation in pre-clinical settings. Here we report, a novel genetically engineered mice which may represents a preclinical model of human diastolic dysfunction to some extent. Topoisomerase 2 beta (Top2b) is an important enzyme in transcriptional activation of some inducible genes through transient double-stranded DNA breakage events around promoter regions. We created a conditional, tissue-specific, inducible Top2b knockout mice in the heart. Serendipitously, echocardiographic parameters and more invasive analysis of left ventricular function with pressure-volume loops show features of diastolic dysfunction. This was also confirmed histologically. At the cellular level, the Top2b knockdown showed morphological changes and molecular signaling akin to human diastolic dysfunction. Reverse phase protein analysis showed activation of p53 and inhibition of, Akt, as the possible mediators of diastolic dysfunction. Finally, activation of p53 and inhibition of Akt were confirmed in myocardial biopsy samples obtained from human diastolic dysfunctional hearts. Thus, we report for the first time, a Top2b downregulated preclinical mice model for diastolic dysfunction which demonstrates that Akt and p53 are the possible mediators of the pathology, hence representing novel and viable targets for future therapeutic interventions in diastolic dysfunction.

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Lithium-sulfur (Li-S) cells are emerging as the dominant constituents of the next generation battery technology, offering high theoretical capacity around 1675 mA h g-1 and the additional advantages of low cost and non-toxic nature. Activated carbon, derived from natural resources is being extensively investigated for applications as electrode materials in high power supercapacitors and for making composite electrodes for designing high energy density electrochemical cells. The present work is aimed at introducing the potential of the composite cathode of sulfur with the biomass-derived, steam activated carbon (AC) along with the free-standing and flexible film of carbon nanotubes as the interlayer for designing efficient Li-S cells. The composite obtained by impregnating sulfur particles into the pores of coconut shell derived and steam activated carbon, subjected to efficient acid washing procedures to attain maximum purity, called as the activated carbon-sulfur (ACS) is used as the composite cathode material. The flexible film of acid-functionalized carbon nanotubes termed as the CNTF placed between the composite cathode and the separator material serves as an active interlayer to boost the performance efficiency of the assembled Li-S cells. The ACS composite is synthesized by the solvothermal method, and the flexible CNTF is obtained by solution casting. The Li-S cells assembled with the ACS composite as the active cathode material and the CNTF as the interlayer are found to exhibit quite impressive discharge capacity and cycling stability. These cells deliver an initial discharge capacity of 1562 mA h g-1 at 0.05 C rate and retain 71% of the initial capacity at 1 C rate after 200 cycles. The conducting and the porous network of the ACS helps to enhance the overall electrical conductivity of the sulfur composite cathode and the highly conducting CNTF interlayer accelerates the electrochemical activity taking place in the cell. The interlayer restricts the polysulfides from migrating to the anode and thereby suppresses the polysulfide shuttle phenomenon. The use of the coconut shell derived, steam activated and acid washed carbon for making the composite cathode with sulfur and the CNTF interlayer, obtained by the acid functionalization of carbon nanotubes is a novel approach to realize Li-S cells with high capacity and excellent cycling stability, which has not yet been pursued in detail.

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BACKGROUND: Patients with massive and submassive pulmonary embolism (PE) require rapid identification, triage, and consideration for reperfusion therapy. Use of an existing ST-segment elevation myocardial infarction (STEMI) team and activation protocol may be an effective means to care for these patients. OBJECTIVE: The objective of this analysis was to evaluate a pilot study using the STEMI team and a dedicated PE protocol for treatment of patients with massive and submassive PE. METHODS: From June 2014 to April 2016, a total of 40 patients with massive and submassive PE were evaluated. Baseline demographics, mode of hospital entry (transfer-in, in-hospital, and emergency department [ED] arrival), treatment time intervals (door to computed tomography PE protocol [CTPE], CTPE to invasive pulmonary angiogram, door to treatment time), procedures performed, and in-hospital clinical events were collected. RESULTS: Mean age was 56 ± 14 years, 17 (42%) were male, and 12 (30%) had a prior history of deep venous thrombosis or PE. Twenty-three patients (57%) had massive PE and 17 patients (43%) had submassive PE. Mode of hospital entry was transfer-in (38%), in-hospital (20%), and ED arrival (42%). Four patients (10%) presented with cardiac arrest, 8 patients (20%) required intubation, and 5 patients (12%) required extracorporeal membrane oxygenation. Ten patients (25%) received anticoagulation therapy or placement of inferior vena cava filter, 3 patients (7.5%) received diagnostic pulmonary angiography alone, and 27 patients (67.5%) received endovascular treatment. For patients arriving via the ED, door to CTPE was 4.9 ± 3.6 hours, CTPE to diagnostic pulmonary angiography was 7.8 ± 8.5 hours, and door to treatment time was 10.2 ± 9.0 hours. Endovascular devices utilized included combinations of rheolytic and other thrombectomy devices as well as catheter-directed fibrinolysis. Length of hospital stay was 15 ± 15 days and in-hospital survival rate was 90%. CONCLUSIONS: Use of an existing STEMI team and activation protocol is a feasible method to care for patients with massive and submassive PE. This pilot study demonstrated rapid treatment times with low in-hospital mortality.

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Primary hypertension is a major risk factor for ischemic heart disease, stroke, and chronic kidney disease. Insights obtained from the study of rare Mendelian forms of hypertension have been invaluable in elucidating the mechanisms causing primary hypertension and development of antihypertensive therapies. Endothelial cells play a key role in the regulation of blood pressure; however, a Mendelian form of hypertension that is primarily due to endothelial dysfunction has not yet been described. Here, we show that the urea cycle disorder, argininosuccinate lyase deficiency (ASLD), can manifest as a Mendelian form of endothelial-dependent hypertension. Using data from a human clinical study, a mouse model with endothelial-specific deletion of argininosuccinate lyase (Asl), and in vitro studies in human aortic endothelial cells and induced pluripotent stem cell-derived endothelial cells from individuals with ASLD, we show that loss of ASL in endothelial cells leads to endothelial-dependent vascular dysfunction with reduced nitric oxide (NO) production, increased oxidative stress, and impaired angiogenesis. Our findings show that ASLD is a unique model for studying NO-dependent endothelial dysfunction in human hypertension.

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As tissue engineering continues to mature, it is necessary to develop new technologies that bring insight into current paradigms and guide improvements for future experiments. To this end, we have developed a system to characterize our bioartificial heart model and compare them to functional native structures. In the present study, the hearts of adult Sprague-Dawley were decellularized resulting in a natural three-dimensional cardiac scaffold. Neonatal rat primary cardiac cells were then cultured within a complex 3D fibrin gel, forming a 3-dimensional cardiac construct, which was sutured to the acellular scaffold and suspended in media for 24-48 h. The resulting bioartificial hearts (BAHs) were then affixed with 16 electrodes, in different configurations to evaluate not only the electrocardiographic characteristics of the cultured tissues, but to also test the system's consistency. Histological evaluation showed cellularization and cardiac tissue formation. The BAHs and native hearts were then evaluated with our 16-channel flexible system to acquire the metrics associated with their respective electrophysiological properties. Time delays between the native signals were in the range of 0-95 ms. As well, color maps revealed a trend in impulse propagation throughout the native hearts. After evaluation of the normal rat QRS complex we found the average amplitude of the R-wave to be 5351.48 ± 44.92 µV and the average QRS duration was found to be 10.61 ± 0.18 ms. In contrast, BAHs exhibited more erratic and non-uniform activity that garnered no appreciable quantification. The data collected in this study proves our system's efficacy for EKG data procurement.

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Framingham Heart Study suggests that dysfunction of steroid receptor coactivator-1 may be involved in the development of hypertension. However, there is no functional evidence linking steroid receptor coactivator-1 to the regulation of blood pressure. We used immunohistochemistry to map the expression of steroid receptor coactivator-1 protein in mouse brain, especially in regions implicated in the regulation of blood pressure. Steroid receptor coactivator-1 protein was found in central amygdala, medial amygdala, supraoptic nucleus, arcuate nucleus, ventromedial, dorsomedial, paraventricular hypothalamus, and nucleus of the solitary tract. To determine the effects of steroid receptor coactivator-1 protein on cardiovascular system we measured blood pressures, blood flow velocities, echocardiographic parameters, and aortic input impedance in female steroid receptor coactivator-1 knockout mice and their wild type littermates. Steroid receptor coactivator-1 knockout mice had higher blood pressures and increased aortic stiffness when compared to female wild type littermates. Additionally, the hearts of steroid receptor coactivator-1 knockout mice seem to consume higher energy as evidenced by increased impedance and higher heart rate pressure product when compared to female wild type littermates. Our results demonstrate that steroid receptor coactivator-1 may be functionally involved in the regulation of blood pressure and aortic stiffness through the regulation of sympathetic activation in various neuronal populations.

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